POS0314 IDENTIFICATION OF CIRCULATING microRNA SIGNATURES IN PATIENTS WITH PSORIASIS WITH SUBCLINICAL JOINT DISEASE AND PATIENTS WITH PSORIATIC ARTHRITIS
Authors: J. Haschka, D. Simon, S. Bayat, Z. Messner, E. Kampylafka, F. Fagni, S. Skalicky, M. Hackl, H. Resch, J. Zwerina, A. Kleyer, M. Sticherling, G. Schett, R. Kocijan, J. Rech
Journal: Annals of the Rheumatic Diseases (2022)

Background MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression. Specific miRNA signatures have been identified in numerous diseases and may serve as potential biomarkers or new drug targets. Whether certain miRNA signatures are associated with psoriatic joint disease is currently unknown. Objectives To search for circulating miRNA signatures in psoriasis patients with subclinical joint disease and in patients with psoriatic arthritis (PsA). Methods Analyses of serum miRNA were done in three groups: (1) PsA patients fulfilling CASPAR criteria (PsA), (2) healthy controls without past or present signs of musculoskeletal disease (HC) and (3) psoriasis patients with musculoskeletal pain but no signs of clinical PsA (PsO). PsO and PsA patients received a hand MRI, which was scored according to PsAMRIS method. miRNA analysis of serum samples was performed stepwise using RT-qPCR (TAmiRNA Vienna). In the discovery phase 192 miRNA assays were analyzed in 48 samples (N=16 each group). In the validation phase 17 miRNAs (Table 1) were selected and analyzed in 94 samples (N=35 PsA, N=24 PsO, N=35 HC) based on results of discovery phase and previous reports in literature. Results presented as mean±SD/median (IQR), p-values are adjusted for multiple testing. Table 1. miRNAs PsA vs HC PsO vs HC PsA vs PsO Discovery Phase Validation Phase Discovery Phase Validation Phase Discovery Phase Validation Phase p-adj. p-adj. p-adj. p-adj. p-adj. p-adj. miR-93-5p 0.0001 &lt;0.001 0.008 0.005 0.039 0.947 miR-29b-3p 0.0001 &lt;0.0001 0.004 0.0002 0.191 0.522 miR-19b-3p 0.007 0.708 0.0002 0.020 0.138 0.147 miR-320d 0.001 0.619 &lt;0.0001 0.135 0.941 0.247 miR-144-5p 0.003 0.006 0.0001 0.169 0.350 0.444 miR-188-5p 0.014 0.990 0.975 0.647 0.053 0.839 let-7b-5p 0.025 0.0003 0.889 0.026 0.0003 0.472 miR-92a-3p 0.043 0.001 0.005 0.773 &lt;0.0001 0.0005 miR-324-3p 0.138 1.000 0.257 0.392 0.814 0.518 miR-126-3p 0.014 0.169 0.013 0.598 0.922 0.654 miR-223-3p 0.169 0.872 0.617 0.746 0.519 1.000 miR-130a-3p 0.039 0.035 0.556 0.009 0.006 0.724 miR-140-3p 0.350 0.053 0.002 0.006 0.118 0.683 miR-155-5p 0.159 0.995 0.169 0.549 0.922 0.604 miR-21-5p 0.297 0.990 0.003 0.116 0.08 0.014 miR-146a-5p 0.706 0.004 0.836 0.038 0.905 0.941 miR-122-5p 0.960 0.734 0.695 0.799 0.905 0.444 Results 51 PsA patients (age: 51.3±11.4 years; 56.9% females), 40 PsO patients (51.4±11.0; 37.5%) and 50 HC (51.0±10.5; 52.9%) were assessed. Duration of psoriasis was 12(25) years in PsA and 15(22.8) years in PsO. Duration of joint disease in PsA was 1.0(4.8) year. 51% of PsA and 5% of PsO patients were on biological disease modifying drugs (bDMARDs), 49% vs. 10% on conventional DMARDs. The most frequent findings in the MRI were erosions (PsA 59.6%; PsO 40%) and synovitis (PsA 48.9%; PsO 42.5%). PsA patients had higher number of tenosynovitis compared to PsO (p=0.04). In discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared to HC, with an overlap of 33 miRNAs changed in PsA and PsO (p&lt;0.05). Results of the selected 17 miRNAs are presented in Table 1. The top candidates to differentiate PsA and HC were miR-29b-3p (AUC=0.87), miR-93-5p (AUC=0.83) and let-7b-5p (AUC=0.79). For differentiating PsO and HC, they were miR-29b-3p (AUC=0.82), miR-140-3p (AUC=0.81) and miR-19b-3p (AUC=0.80) and for PsO vs. PsA miR-92a-3p (AUC=0.87), let-7b-5p (AUC=0.72) and miR-21-5p (AUC=0.70). miR-93-5p was lower in patients with erosions (p=0.01). miR-92a-3p, let-7b-5p and miR-21-5p were lower in patients with tenosynovitis, bone proliferations or erosions. Conclusion PsA and PsO patients show miRNA signatures different from HC. Top candidate miRNAs differentially regulated in PsA and PsO have been previously reported in alteration of bone metabolism and osteoarthritis indicating the intimate association of psoriatic inflammation with bone and cartilage changes. References [1]Faustini F et al. Ann Rheum Dis 2016 Dec;75(12):2068-2074 [2]Hackl, M et al. Molecular and Cellular Endocrinology Elsevier Ireland Ltd 432, pp 83–95 [3]Feichtinger X et al. Sci Rep 2018 Mar 20;8(1):4867 Disclosure of Interests None declared